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Biomedical subjects

Y Itoh

Publications and source records attributed to Y Itoh.

At least 91 records · Page 5Linked to original sources
PubMed2001

Increase of chemokine interferon-inducible protein-10 (IP-10) in the serum of patients with autoimmune liver diseases and increase of its mRNA expression in hepatocytes.

To clarify the role of IP-10 in autoimmune liver diseases, we studied the serum levels of IP-10 in 14 patients with autoimmune hepatitis (AIH), 23 patients with primary biliary cirrhosis (PBC), and 65 patients with chronic viral hepatitis (20 type B and 45 type C). The hepatic expression of IP-10 mRNA and the correlation between the serum levels of IP-10 and clinical parameters were also evaluated. In addition to 20 healthy controls, 16 rheumatoid arthritis (RA) patients were included as an extrahepatic inflammatory disease. The serum level of IP-10 was significantly (P < 0.02) higher in patients with AIH, PBC, and chronic hepatitis B and C than in healthy controls, and it was significantly correlated (P < 0.05) with the serum levels of aspartate aminotransferase and alanine aminotransferase in patients with AIH, PBC, and chronic hepatitis B and C. The serum level of IP-10 was not elevated in RA patients. After successful treatment of AIH and chronic hepatitis C, the serum level of IP-10 decreased to the same level as in healthy volunteers. As we previously showed in cases with chronic hepatitis B or C, in situ hybridization in both AIH and PBC cases demonstrated the expression of IP-10 mRNA in hepatocytes around focal or lobular necrosis surrounded by infiltrating mononuclear cells, whereas IP-10 mRNA was not expressed in areas around the damaged bile ducts in PBC cases. The present results suggest that IP-10 is specifically produced by hepatocytes in inflammatory areas irrespective of the aetiology of hepatitis, and that IP-10 may help to recruit T cells to the hepatic lesions in autoimmune liver diseases as well as in chronic viral hepatitis.

Autoimmune Diseases↗
PubMed2001

Clinical significance of elevated serum interferon- inducible protein-10 levels in hepatitis C virus carriers with persistently normal serum transaminase levels.

The aim of this study was to assess the immunological profile in hepatitis C virus carriers with persistently normal serum transaminase levels. Forty-two serum HCV RNA positive patients with persistently normal serum transaminase levels (22 natural 'asymptomatic HCV carriers' and 20 biochemical responders to IFN therapy) and 23 complete responders to IFN therapy were enrolled. The HCV genotypes and serum HCV RNA levels were determined before IFN therapy in treatment responders, and at entry in the others. The serum levels of IFN-inducible protein-10 (IP-10) (a protein mainly induced by IFN-gamma), interleukin (IL)-10, and IL-4 were measured in all patients while the serum transaminase levels were normal. The serum transaminase levels and platelet counts were then monitored for the next 4 years and the changes in liver fibrosis were assessed. The serum levels of IP-10 in infected and biochemically normal patients were significantly higher than the levels in complete responders to therapy, whereas the serum levels of IL-10 and IL-4 did not vary significantly among the different groups. During the 4-year follow-up period, 10/20 (50%) biochemical responders and 12/22 (55%) asymptomatic carriers had an elevation of the serum transaminase levels. A significant (P=0.0370) increase in platelet count after 4 years and improvement in liver fibrosis were noted in treatment responders but not in infected patients. The weak but significant residual immune response as reflected by the increased serum IP-10 level may underlie the outcome of HCV carriers with persistently normal serum transaminase levels.

Alanine Transaminase↗
PubMed2001

The CbrA-CbrB two-component regulatory system controls the utilization of multiple carbon and nitrogen sources in Pseudomonas aeruginosa.

A novel two-component system, CbrA-CbrB, was discovered in Pseudomonas aeruginosa; cbrA and cbrB mutants of strain PAO were found to be unable to use several amino acids (such as arginine, histidine and proline), polyamines and agmatine as sole carbon and nitrogen sources. These mutants were also unable to use, or used poorly, many other carbon sources, including mannitol, glucose, pyruvate and citrate. A 7 kb EcoRI fragment carrying the cbrA and cbrB genes was cloned and sequenced. The cbrA and cbrB genes encode a sensor/histidine kinase (Mr 108 379, 983 residues) and a cognate response regulator (Mr 52 254, 478 residues) respectively. The amino-terminal half (490 residues) of CbrA appears to be a sensor membrane domain, as predicted by 12 possible transmembrane helices, whereas the carboxy-terminal part shares homology with the histidine kinases of the NtrB family. The CbrB response regulator shows similarity to the NtrC family members. Complementation and primer extension experiments indicated that cbrA and cbrB are transcribed from separate promoters. In cbrA or cbrB mutants, as well as in the allelic argR9901 and argR9902 mutants, the aot-argR operon was not induced by arginine, indicating an essential role for this two-component system in the expression of the ArgR-dependent catabolic pathways, including the aruCFGDB operon specifying the major aerobic arginine catabolic pathway. The histidine catabolic enzyme histidase was not expressed in cbrAB mutants, even in the presence of histidine. In contrast, proline dehydrogenase, responsible for proline utilization (Pru), was expressed in a cbrB mutant at a level comparable with that of the wild-type strain. When succinate or other C4-dicarboxylates were added to proline medium at 1 mM, the cbrB mutant was restored to a Pru+ phenotype. Such a succinate-dependent Pru+ property was almost abolished by 20 mM ammonia. In conclusion, the CbrA-CbrB system controls the expression of several catabolic pathways and, perhaps together with the NtrB-NtrC system, appears to ensure the intracellular carbon: nitrogen balance in P. aeruginosa.

Amino Acid Sequence↗
PubMed2001

A novel heat stress-responsive gene in the marine diatom Chaetoceros compressum encoding two types of transcripts, a trypsin-like protease and its related protein, by alternative RNA splicing.

We investigated the change of mRNA expression patterns in the laboratory-grown diatom Chaetoceros compressum under heat-stress conditions by mRNA arbitrarily primed (RAP) RT-PCR. Cells grown at 20 degrees C were subjected to heat treatment at 30 degrees C for 15 min and subsequently maintained at 20 degrees C for 8 h. Four genes including HI-5 were detected as heat stress-responsive genes by fingerprint analysis of RAP RT-PCR. Cloning for full-length cDNA sequences of HI-5 transcripts and related genomic DNA analysis revealed that two types of mRNA, HI-5a and HI-5b, were transcribed from the single HI-5 gene. While the HI-5a protein contained a catalytic domain characteristic to trypsin-like proteases, the HI-5b protein lacked this domain due to an insertion in the associated mRNA of 112 nucleotides; this insertion sequence contained a stop codon near the central region. Quantitative RT-PCR was performed to investigate the changes in expression levels of the two types of mRNA following heat treatment. The HI-5b transcripts were constitutively expressed in both unstressed and heat-stressed cells. In contrast, the number of HI-5a transcripts markedly increased in cells immediately after heat stress, reaching levels 19-fold higher at 8 h after heat stress than that in unstressed cells. These results suggest that RNA splicing plays a key role in heat stress-dependent expression of the HI-5a and HI-5b transcripts from the single HI-5 gene in the diatom.

Alternative Splicing↗
PubMed2001

Local and global cerebral blood flow and glucose utilization in the alpha-galactosidase A knockout mouse model of Fabry disease.

Fabry disease is an X-linked lysosomal disorder characterized by deficient alpha-galactosidase A activity and intracellular accumulations of glycosphingolipids, mainly globotriaosylceramide (Gb3). Clinically, patients occasionally present CNS dysfunction. To examine the pathophysiology underlying brain dysfunction, we examined glucose utilization (CMR(glc)) and cerebral blood flow (CBF) globally and locally in 18 brain structures in the alpha-galactosidase A gene knockout mouse. Global CMR(glc) was statistically significantly reduced by 22% in Fabry mice (p < 0.01). All 18 structures showed decreases in local CMR(glc) ranging from 14% to 33%. The decreases in all structures of the diencephalon, caudate-putamen, brain stem, and cerebellar cortex were statistically significant (p < 0.05). Global cerebral blood flow (CBF) and local CBF measured in the same 18 structures were lower in Fabry mice than in control mice, but none statistically significantly. Histological examination of brain revealed no cerebral infarcts but abundant Gb3 deposits in the walls of the cerebral vessels with neuronal deposits localized to the medulla oblongata. These results indicate an impairment in cerebral energy metabolism in the Fabry mice, but one not necessarily due to circulatory insufficiency.

Animals↗
PubMed2001

Analysis of methicillin-resistant Staphylococcus aureus isolates by proton magnetic resonance spectroscopy.

OBJECTIVES: To evaluate the stability and(1)H nuclear magnetic resonance ((1)H NMR) differences among bacterial strains, we analysed(1)H NMR spectra for 50 methicillin-resistant Staphylococcus aureus (MRSA) isolates from 42 patients. METHODS: (1)H NMR spectra for 50 MRSA isolates were obtained at 30 degrees C using a JNM-GX 270 NMR spectrometer at a field strength of 6.34 Tesla (270 MHz for(1)H). DNA fingerprints were obtained by pulsed-field gel electrophoresis (PFGE). RESULTS: Each strain had eight to nine specific resonance features in the 0.5-4.5 ppm spectral region. These features were found in all strains, but the intensity of each feature varied between strains. Six resonance features (A-F) were selected for investigation. The relative integrated intensity (mean+/-SD, normalized to feature C = 1) of each feature was: feature A, 0.49+/-0.16; feature B, 3.93+/-0.81; feature D, 0.38+/-0.22; feature E, 1.51+/-0.96; feature F, 2.18+/-0.47. Within-strain reproducibility of feature intensities for A, B, D and F was good (coefficient of variation < 10%) for replicate cultures, analyzed on separate days. Feature E showed poor within-strain reproducibility. Storage at 4 degrees C for 4 months or disintegration of the micro-organisms by ultrasound did not alter(1)H NMR spectra. Two isolates from different patients, but the same hospital, showed indistinguishable NMR spectra, and were also indistinguishable in PFGE. Five strains with distinct PFGE patterns showed differences in NMR spectra outside the range of within-strain variation. CONCLUSIONS: It is possible to analyse the whole molecular structure of MRSA by(1)H NMR. With this technique, we established that there are detectable, reproducible differences in quantitative cell composition between MRSA strains.(1)H NMR spectroscopy appears to have potential as a useful tool for epidemiological typing of bacteria.

DNA Fingerprinting↗
PubMed2001

Histopathological analyses of silent pituitary somatotroph adenomas using immunohistochemistry, in situ hybridization and confocal laser scanning microscopic observation.

To characterize the morphological and functional aspects of silent somatotroph adenomas with paradoxical responses of GH in TRH or GnRH provocation tests, which are considered to be a useful strategy for endocrinological identification of silent somatotroph adenomas, we examined three silent somatotroph adenomas histopathologically. The adenomas were investigated by immunohistochemistry, including the highly sensitive catalyzed signal amplification system, the non-radioisotopic in situ hybridization method, and confocal laser scanning microscopy. GH production and GH-immunopositive secretory granules in the adenoma cells were demonstrated histopathologically, and the adenomas were interpreted as being densely granulated somatotroph adenomas. Endocrinological identification of silent somatotroph adenomas in combination with paradoxical responses of GH in TRH or GnRH provocation tests may elucidate the increasing number of silent somatotroph adenomas that have been regarded as mammotroph or clinically inactive adenomas. One should be aware of the differences between the previously reported silent somatotroph adenomas, most of which are sparsely granulated somatotroph adenomas, a somatotroph adenomas with paradoxical and the silent somatotroph adenomas, most of which are sparsely granulated somatotroph adenomas, and the silent somatotroph adenomas with paradoxical responses of GH in TRH or GnRH provocation tests, which are densely granulated somatotroph adenomas.

Adenoma, Chromophobe↗
PubMed2001

Time course profile and cell-type-specific production of monokine induced by interferon-gamma in Concanavalin A-induced hepatic injury in mice: comparative study with interferon-inducible protein-10.

BACKGROUND: We have previously shown that interferon-inducible protein-10 (IP-10), a chemokine for activated lymphocytes, was specifically induced in the liver of Concanavalin A (Con A)-treated mice. The aim of this study was to investigate the time course profile and cell-type-specific hepatic production of monokine induced by interferon-gamma (MIG), a chemokine which shares its receptor and most of its activity with IP-10, in Con A-treated mice and to compare them with those of IP-10. METHODS: Hepatic mRNA expression of MIG and IP-10 was studied by means of Northern blot analysis and in situ hybridization in Con A-treated mice. The levels of MIG and IP-10 in the serum and culture supernatants of murine hepatoma-, hepatic sinusoidal endothelial cell-, hepatic stellate cell- and macrophage-derived cell lines were determined by means of specific enzyme-linked immunosorbent assays. RESULTS: The serum level of MIG slowly reached a maximum at 12 h after Con A injection and remained elevated for a long time, whereas that of IP-10 reached a maximum at 3 h and declined quickly, a finding supported by Northern blot analysis. Using in situ hybridization, the mRNA of MIG as well as IP-10 was found to be expressed in hepatocytes and hepatic non-parenchymal cells. Similar to IP-10, MIG was produced by hepatoma-, hepatic sinusoidal endothelial cell-, hepatic stellate cell- and macrophage-derived cell lines in vitro. CONCLUSIONS: Although both MIG and IP-10 were produced by hepatocytes and hepatic non-parenchymal cells in Con A-treated mice, the time course profile of MIG was distinguishable from that of IP-10. The fact that hepatic MIG and IP-10 were produced sequentially in this hepatitis model may suggest that a non-redundant role is played by these two chemokines in the process of hepatic necro-inflammation.

Animals↗
PubMed2001

Pancreaticobiliary arteriovenous malformation with common bile duct dilation in a patient with hemobilia.

Arteriovenous malformation of the pancreas is a very rare entity. We describe a case involving the head of the pancreas associated with progressive hemobilia bleeding from the lower part of the common bile duct. The patient was a 50-year-old man with acute epigastralgia. Endoscopic retrograde cholangiopancreatography revealed hemobilia and cystic dilation of the common bile duct. Angiography demonstrated increased blood volume in the head of the pancreas and early filling of the superior mesenteric and portal veins. Abdominal pain and progressive anemia caused by hemobilia required surgical treatment. Histologic examination of the resected specimen revealed marked proliferation of the blood vessels in the pericholedochal area and the exact point of bleeding from the pancreaticobiliary arteriovenous malformation.

Angiography↗
PubMed2001

Post-resuscitative hypothermic bypass reduces ischemic brain injury in swine.

OBJECTIVES: Increasing human and laboratory evidence suggests that post-resuscitative brain hypothermia reduces the pathologic consequences of brain ischemia. Using a swine model of prolonged cardiac arrest, this investigation sought to determine whether unilateral hypothermic carotid bypass was capable of inducing selective brain hypothermia and reducing neurohistologic damage. METHODS: Ventricular fibrillation was induced in common swine (n = 12). After 20 minutes of cardiopulmonary arrest (without ventilatory support or cardiopulmonary resuscitation), systemic extracorporeal bypass was instituted to restore coronary and cerebral perfusion, followed by restoration of normal sinus rhythm. Animals randomized to the normal brain temperature (NBT) cohort received mechanical ventilation and intravenous fluids for 24 hours. The selective brain hypothermia (SBH) cohort received 12 hours of femoral/carotid bypass at 32 degrees C. The bypass temperature was then increased one degree per hour until reaching 37 degrees C and continued at this temperature until completion of the protocol (24 hours). Histopathologic damage was evaluated in two areas of the hippocampus. RESULTS: Normal sinus rhythm was restored in all animals after the systemic (femoral/femoral) bypass was initiated. Nasal temperature (surrogate measure of brain temperature) remained higher than 37.0 degrees C throughout the 24-hour recovery period in the NBT animals. In the SBH cohort, right nasal temperature dropped to the mild hypothermic range (<34 degrees C) two hours after institution of femoral/carotid bypass. This was maintained throughout the 12-hour cooling period without hemodynamic compromise. There was a significant improvement in the neurohistology scores in the CA1 region of the hippocampus of the SBH treated animals as compared with those of the NBT cohort. CONCLUSIONS: Post-resuscitative selective brain hypothermia reduced regional ischemic brain damage in swine with prolonged ventricular fibrillation.

Animals↗
PubMed2001

Rapid development of brain hypothermia using femoral-carotid bypass.

OBJECTIVES: Advances in the field of cardiopulmonary resuscitation have led to an increasing number of patients initially surviving sudden cardiac arrest. Unfortunately, most of these patients do not recover from the resultant anoxic brain insult. Several animal and human trials have suggested that post-resuscitative brain hypothermia may improve neurologic recovery after cardiopulmonary arrest. Present cooling methods are slow, induce only brain surface cooling, or result in systemic hypothermia. The authors tested the hypothesis that unilateral hypothermic carotid bypass would induce bilateral brain cooling without evoking systemic hypothermia or hemodynamic instability. METHODS: Anesthetized, ventilated common swine (n = 6, 24-37 kg) underwent right femoral and carotid artery bypass cannulation. Central and peripheral hemodynamic parameters were recorded every 2 minutes throughout the procedure. Thermodynamic parameters included bilateral frontal lobe, bilateral nasopharyngeal, pulmonary artery, and rectal temperatures. Hypothermic femoral-carotid bypass was accomplished by drawing blood from the right femoral artery, cooling it to 24 degrees C, and returning it to the right carotid artery at a flow rate of 5 mL/kg/min for 30 minutes. RESULTS: With initiation of cooling, brain temperatures dropped rapidly from baseline of 37.2 degrees C to 30.6 degrees C (right frontal lobe) and 33.1 degrees C (left frontal lobe) at 30 minutes. Pulmonary artery and rectal temperatures also decreased, but never reached mild hypothermic levels (34 degrees C). There was no significant change in any hemodynamic parameters during brain cooling. CONCLUSIONS: Femoral-carotid hypothermic bypass rapidly induced a state of selective brain hypothermia without causing systemic hypothermia or hemodynamic instability.

Analysis of Variance↗
PubMed2001

Specificity and genetic polymorphism of the Bacillus competence quorum-sensing system.

A quorum-sensing mechanism involving the pheromone ComX and the ComP-ComA two-component system controls natural competence in Bacillus subtilis. ComX is expressed as a cytoplasmic inactive precursor that is released into the extracellular medium as a cleaved, modified decapeptide. This process requires the product of comQ. In the presence of ComX, the membrane-localized ComP histidine kinase activates the response regulator ComA. We compared the sequences of the quorum-sensing genes from four closely related bacilli, and we report extensive genetic polymorphism extending through comQ, comX, and the 5' two-thirds of comP. This part of ComP encodes the membrane-localized and linker domains of the sensor protein. We also determined the sequences of the comX genes of four additional wild-type bacilli and tested the in vivo activities of all eight pheromones on isogenic strains containing four different ComP receptor proteins. A striking pattern of specificity was discovered, providing strong evidence that the pheromone contacts ComP directly. Furthermore, we show that coexpression of comQ and comX in Escherichia coli leads to the production of active pheromone in the medium, demonstrating that comQ is the only dedicated protein required for the processing, modification, and release of active competence pheromone. Some of the implications of these findings for the evolution and the mechanism of the quorum-sensing system are discussed.

Amino Acid Sequence↗
PubMed2001

Molecular characterization and regulation of the aguBA operon, responsible for agmatine utilization in Pseudomonas aeruginosa PAO1.

Pseudomonas aeruginosa PAO1 utilizes agmatine as the sole carbon and nitrogen source via two reactions catalyzed successively by agmatine deiminase (encoded by aguA; also called agmatine iminohydrolase) and N-carbamoylputrescine amidohydrolase (encoded by aguB). The aguBA and adjacent aguR genes were cloned and characterized. The predicted AguB protein (M(r) 32,759; 292 amino acids) displayed sequence similarity (< or =60% identity) to enzymes of the beta-alanine synthase/nitrilase family. While the deduced AguA protein (M(r) 41,190; 368 amino acids) showed no significant similarity to any protein of known function, assignment of agmatine deiminase to AguA in this report discovered a new family of carbon-nitrogen hydrolases widely distributed in organisms ranging from bacteria to Arabidopsis. The aguR gene encoded a putative regulatory protein (M(r) 24,424; 221 amino acids) of the TetR protein family. Measurements of agmatine deiminase and N-carbamoylputrescine amidohydrolase activities indicated the induction effect of agmatine and N-carbamoylputrescine on expression of the aguBA operon. The presence of an inducible promoter for the aguBA operon in the aguR-aguB intergenic region was demonstrated by lacZ fusion experiments, and the transcription start of this promoter was localized 99 bp upstream from the initiation codon of aguB by S1 nuclease mapping. Experiments with knockout mutants of aguR established that expression of the aguBA operon became constitutive in the aguR background. Interaction of AguR overproduced in Escherichia coli with the aguBA regulatory region was demonstrated by gel retardation assays, supporting the hypothesis that AguR serves as the negative regulator of the aguBA operon, and binding of agmatine and N-carbamoylputrescine to AguR would antagonize its repressor function.

Agmatine↗
PubMed2001

Regional differences in mechanisms of cerebral circulatory response to neuronal activation.

Vibrissal stimulation raises cerebral blood flow (CBF) in the ipsilateral spinal and principal sensory trigeminal nuclei and contralateral ventroposteromedial (VPM) thalamic nucleus and barrel cortex. To investigate possible roles of adenosine and nitric oxide (NO) in these increases, local CBF was determined during unilateral vibrissal stimulation in unanesthetized rats after adenosine receptor blockade with caffeine or NO synthase inhibition with N(G)-nitro-L-arginine methyl ester (L-NAME) or 7-nitroindazole (7-NI). Caffeine lowered baseline CBF in all structures but reduced the percent increase during stimulation only in the two trigeminal nuclei. L-NAME and 7-NI lowered baseline CBF but reduced the percent increase during stimulation only in the higher stations of this sensory pathway, i.e., L-NAME in the VPM nucleus and 7-NI in both the VPM nucleus and barrel cortex. Combinations of caffeine with 7-NI or L-NAME did not have additive effects, and none alone or in combination completely eliminated functional activation of CBF. These results suggest that caffeine-sensitive and NO-dependent mechanisms are involved but with different regional distributions, and neither fully accounts for the functional activation of CBF.

Animals↗
PubMed2001

Alteration of endothelin-1 concentration in STZ-induced diabetic rat nephropathy. Effects of a PGI(2) derivative.

BACKGROUND: Recently, an endothelin (ET-1) with a potent vasoconstrictive activity and stimulative activity of vascular muscular cell growth was discovered and blood ET-1 levels were higher in diabetic patients than in healthy subjects, suggesting that high ET-1 levels assist development and progression of diabetic microangiography. METHODS: We examined renal function, and serum and tissue ET-1 levels in streptozotocin (STZ)-induced diabetic rats treated with a prostaglandin (PG) I(2) derivative to investigate the effect of PGI(2) in diabetic vascular disturbance. RESULTS: Renal weight, urinary albumin, urinary N-acetyl-beta,D-glucosaminidase (NAG) and serum ET-1 levels increased in STZ-induced diabetic rats, and a tendency to increase in renal tissue ET-1 levels was observed. Furthermore, electron-microscopic findings in the kidneys showed mesangial cell proliferation and mesangial matrix expansion which might be caused by diabetic nephropathy. The PGI(2) derivative reduced urinary albumin and NAG levels in STZ-induced rats. It was considered, therefore, that the PGI(2) derivative is effective in diabetic nephropathy. As the PGI(2) derivative also reduced renal tissue ET-1 levels, improvement of diabetic nephropathy partially was considered to result from the reduction of renal tissue ET-1 levels. CONCLUSION: In STZ-induced rats, increased serum ET-1 levels and a tendency to increase in renal tissue ET-1 levels were associated with increases in urinary albumin and NAG levels, and these levels were decreased by a PGI(2) derivative. These findings suggested that increased ET-1 concentrations assist development and progression of diabetic nephropathy, especially diabetic microangiopathy, and the PGI(2) derivative may be effective for inhibition of diabetic microangiopathy mediated by reduction of ET-1 concentrations.

Albuminuria↗
PubMed2001

Intraspinal implants of fibrin glue containing glial cell line-derived neurotrophic factor promote dorsal root regeneration into spinal cord.

OBJECTIVE: The purpose of this study was to determine whether glial cell line-derived neurotrophic factor (GDNF) delivered intraspinally via a fibrin glue (FG) enhanced regeneration of cut dorsal root (DR). METHODS: FG containing GDNF was inserted into aspiration cavities in the lumbar enlargement of adult rats. The transected L5 DR stump was placed at the bottom of the cavity and sandwiched between the FG and the spinal cord. Regenerated DR axons were labeled with horseradish peroxidase (HRP) or with immunohistochemical methods for calcitonin gene-related peptide (CGRP). RESULTS: Primary afferent axons labeled with HRP regenerated into the spinal cord, received GDNF, and made frequent arborization there. Some of these were myelinated axons that established synapses on intraspinal neuronal profiles. CGRP-immunoreactive DR axons extended into the motor neurons and formed prominent varicosities around their cell bodies. Only a few axons regenerated into the spinal cords given FG without GDNF. CONCLUSIONS: Our results indicate that GDNF enhances regeneration of DR into the adult rat spinal cord and that GDNF may be effectively supplied to the intraspinal injury site via FG. Because the regenerated axons establish synapses on intraspinal neurons, this therapeutic strategy has the potential to help to rebuild spinal reflex circuits interrupted by spinal cord injury.

Animals↗